(A) Synthesis of valeranone and eudesmane. The application of stitching and riveting to the synthesis of the above named systems will allow for smooth and direct conversion of 3-methyl-2-cyclohexenone to these model test systems. This will provide the ground work for synthesis of the more complex, active cytotoxic members of this general group of compounds (i.e., encelin). (B) The hydroazulene studies of this proposal will provide a simple and direct strategy for synthesis of both groups ("Type A": Ambrosin, Damsin, etc. and "Type B": Helenalin and Fastigilin C) of active pseudoguaianolide compounds. This strategy will also provide the basis for synthesis of more complex (oxygenated) members of this sesquiterpene group of compounds (i.e., Fastigilan C). Chemical Significance: The testing of "stitching and riveting" as a technique or strategy for approaching sesquiterpene synthesis is the central most important chemical feature of this proposal. We are proposing to test this technique within the framework of target systems of increasing complexity assessing the value of this technique for very complex natural products. Biological Significance: The first model systems of this study have no strong or influencing activity. However, all of the advanced targets of this synthetic effort are recognized cytotoxic agents that are involved in NCI's testing program at many levels. The activity of many of these compounds are reviewed in references 8, 46 and 59. We might further note that at least one member of this class of compounds is very active against mouse tumor but of low toxicity. As anticancer and antileukemic agents, it is not clear what use these compounds will have, but these great activities must be further pursued.